Therapeutic promise offered by adoptive cellular immunotherapy has focused attention on automated large scale mammalian cell culture instrumentation. One reason for this attention is the enormous logistical difficulties associated with generating sufficient numbers of lymphokine activated killer (LAK) cells, by conventional static culture techniques. This resource has severely limited the application and further development of this new alternative therapy. This Phase II study proposes to examine in detail, the biology and methodology required to effectively cultivate therapeutic lymphoid cells in hollow fiber bioreactor (HFBRX)-based instrumentation. Specific metabolic and immunologic parameters will be defined to improve lymphocyte growth and lytic function in automated perfusion culture. Also, improved methodology )e.g., cell harvest) will be developed for the LAK specific HFBRX flowpath developed during the Phase I project. The proposed research will lead to privately funded Phase II commercialization of a clinical instrument.